The goal of this research is to understand, at a molecular level, the way in which beta-adrenergic receptor, occupied by native catecholamines or agonist drugs, stimulate the adenylate cyclase enzyme, thus increasing intracellular cAMP and eliciting the characteristic physiological effect of catecholamines in the target tissue. In current year 1977-1978, I have demonstrated that occupancy of frog erythrocyte beta-adrenergic receptors by agonists results in an increase in apparent receptor size which cannot be mimicked by receptor occupancy by antagonists but is reversed by guanine nuclotides, agents having multiple regulatory effects on agonist-promoted phenomena in nearly all adenylate cyclase-coupled systems. This increase in receptor size does not represent a physical "coupling" with the adenylate cyclase enzyme and thus may instead reflect 1) agonist-induced receptor clustering or 2) associaton with other components of the adenylate cyclase system or 3) a change in receptor conformation to greater moleclar assymmetry. The goals for 1978-1979 are to elucidate the precise molecular components or interactions responsible for the agonist induced increase in apparent beta-adrenergic receptor size and to develop the appropriate starting materials for pursuing reconstitution of a hormonally sensitive adenylate cyclase in a membrane-free system. Considerable progress on the latter problem was made in the current year development of techniques to solubilize the membrane-bound enzyme in a sufficiently stable form without reliance on pretreatment with irreversible activators e.g. NaF.